20-56370727-A-G

Variant names:

• chr20-56370727-A-G
• rs10485805
• NM_198437.3:c.855-68T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198437.3(AURKA):​c.855-68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,562,218 control chromosomes in the GnomAD database, including 59,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (5571 hom., cov: 32)
  • Exomes 𝑓: 0.25 (53957 hom.)
• Consequence: AURKA NM_198437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 15 publications found

Genes affected

AURKA (HGNC:11393): (aurora kinase A) The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

AURKA Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	NM_198437.3	MANE Select	c.855-68T>C		intron	N/A	NP_940839.1	O14965
	AURKA	NM_001424418.1		c.957-68T>C		intron	N/A	NP_001411347.1
	AURKA	NM_001424419.1		c.957-68T>C		intron	N/A	NP_001411348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AURKA	ENST00000395915.8	TSL:1 MANE Select	c.855-68T>C		intron	N/A	ENSP00000379251.3	O14965
	AURKA	ENST00000312783.10	TSL:1	c.855-68T>C		intron	N/A	ENSP00000321591.6	O14965
	AURKA	ENST00000347343.6	TSL:1	c.855-68T>C		intron	N/A	ENSP00000216911.2	O14965

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35896 AN: 151932 Hom.: 5558 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.255 AC: 358963 AN: 1410168 Hom.: 53957 AF XY: 0.256 AC XY: 179563 AN XY: 702312

African (AFR) AF: 0.101 AC: 3264 AN: 32228

American (AMR) AF: 0.497 AC: 20748 AN: 41722

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4664 AN: 25368

East Asian (EAS) AF: 0.760 AC: 29554 AN: 38874

South Asian (SAS) AF: 0.344 AC: 28740 AN: 83534

European-Finnish (FIN) AF: 0.301 AC: 15578 AN: 51792

Middle Eastern (MID) AF: 0.230 AC: 1305 AN: 5670

European-Non Finnish (NFE) AF: 0.224 AC: 239792 AN: 1072382

Other (OTH) AF: 0.261 AC: 15318 AN: 58598

GnomAD4 genome AF: 0.236 AC: 35912 AN: 152050 Hom.: 5571 Cov.: 32 AF XY: 0.247 AC XY: 18334 AN XY: 74320

African (AFR) AF: 0.108 AC: 4475 AN: 41492

American (AMR) AF: 0.371 AC: 5668 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3472

East Asian (EAS) AF: 0.747 AC: 3860 AN: 5166

South Asian (SAS) AF: 0.363 AC: 1753 AN: 4824

European-Finnish (FIN) AF: 0.322 AC: 3401 AN: 10552

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15358 AN: 67960

Other (OTH) AF: 0.245 AC: 518 AN: 2114

Alfa AF: 0.236 Hom.: 9579

Bravo AF: 0.238

Asia WGS AF: 0.499 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10485805; hg19: chr20-54945783;